The metabolic clearance rate (MCR) and hepatic and extrahepatic extraction of progesterone will continue to be studied. The uterine extraction of progesterone will continue to be studied. The uterine extraction of progesterone, estradiol, estrone and androgens and the uterine interconversion of the estrogens and androgens and the uterine conversion of progesterone to 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) and androgens to estrogens will be studied in women during the follicular and luteal phase of the menstrual cycle. These studies will be extended to cases of endometrial hyperplasia and adenocarcinoma of the endometrium. The significance of the circulating concentration of cortisol, which competes with progesterone for transcortin binding, on the MCR of progesterone in women during the menstrual cycle, the third trimester of pregnancy and during labor will be evaluated. The effect of acute and chronic progestin administration on the MCR of progesterone will also be evaluated. These studies will be extended to monkeys where hepatic and extrahepatic extraction of progesterone will be measured in the presence of varying blood concentrations of progesterone or transcortin. The distribution of transcortin will be studied. The question of whether or not transcortin can associate or enter extrahepatic tissues will be examined by preparing radioactively labeled, purified transcortin and incubation of the transcortin with uterine endometrial cells in vitro. These studies augment and supplement the studies presently being carried out in Program Project in Reproductive Biology (HD 07640) to study the distribution, metabolism and mode of action of progesterone.